BACKGROUND: Previous studies of cerebral ischemia have used young animals, with an ischemic time greater than 5 minutes (safe time limit). Despite an increased understanding of neuronal apoptosis, it remains uncertain whether brief cerebral ischemic events of 5 minutes or less damage brain tissue in elderly rodents.OBJECTIVE: To investigate the effects of transient cerebral ischemia (5 minutes)/reperfusion injury on brain cortical and hippocampal edema, aquaporin-4 (AQP-4) expression, and neuronal apoptosis in aged rats, and to compare ischemic sensitivity between cortex and hippocampus.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical School from April 2008 to March 2009.MATERIALS: Rabbit anti-AQP-4 polyclonal antibody, TUNEL kit, and SABC immunohistochemistry kit were purchased from Wuhan Boster Bioengineering, China.METHODS: A total of 160 healthy, male, aged 19-21 months, Wistar rats were randomly assigned to 4 groups: sham-surgery, and ischemia 1-, 3-, and 5-minute groups, with 40 rats in each group.The global cerebral ischemia model was established using the Pusinelli four-vessel occlusion, and the three cerebral ischemia groups were subdivided into reperfusion 12-hour, 1-, 2-, 3-, and 7-day subgroups, with 8 rats in each subgroup. The sham-surgery group was subjected to exposure of the first cervical bilateral alar foramina and bilateral common carotid arteries.MAIN OUTCOME MEASURES: The dry-wet weight assay was used to measure brain water content,and histopathology of the cortex and hippocampus was observed following hematoxylin-eosin staining. In addition, cortical and hippocampal AQP-4 expression was detected by streptavidin-biotin complex immunohistochemistry, and neuronal apoptosis was detected by the TUNEL method.RESULTS: There was no significant difference in brain water content or AQP-4 expression in the cortex and hippocampus between ischemia 1- and 3-minute groups and the sham-surgery group or brain water content or AQP-4 expression in the cortex between ischemia 5-minute group and sham-surgery group (P> 0.05). However, brain water content and AQP-4 expression in the hippocampus after 5 minutes of cerebral ischemia were significantly increased compared with the sham-surgery group (P< 0.05 or P< 0.01). Several TUNEL-positive cells were observed in the cortex and hippocampus of the sham-surgery group and ischemia 1 -minute group, as well as in the cortex of the ischemia 3-minute group. In addition, the number of apoptotic neurons in the hippocampus of ischemia 3-minute group and in the cortex and hippocampus of ischemia 5-minute group was significantly increased (P< 0.05 or P< 0.01). Neuronal apoptosis was increased after 12 hours of ischemia/reperfusion, and it reached a peak by 2 days (P< 0.01).CONCLUSION: Transient cerebral ischemia (5 minutes) resulted in increased hippocampal edema,AQP-4 expression, and neuronal apoptosis. Moreover, cerebral ischemia had a greater effect on neuronal apoptosis than brain edema or AQP-4 expression, and the hippocampus was more sensitive than the cortex.